BACKGROUND: A subcutaneous formulation of infliximab (IFX-SC) approved to treat patients with inflammatory bowel disease may offer improved efficacy versus intravenous infliximab. METHODS: Patients with refractory Crohn's disease (CD, n = 32) previously treated unsuccessfully with at least 2 biologics were treated with IFX-SC and followed from baseline at Week 0 (W0) to Week 30 (W30). The study's primary endpoint was the treatment's persistence at W30, while secondary goals included the analysis of serum infliximab trough levels (TL IFX), dynamics of anti-IFX antibodies (ATIs), and clinical, serum and fecal markers of CD activity during IFX-SC treatment. RESULTS: Midterm treatment persistence with the continuation of treatment after W30 was 53%. TL IFX median values showed rapid, significant upward dynamics and exceeded 15.5 μg/mL at W30, whereas median ATI levels significantly declined. Among ATI-negative patients at W0 (n = 15), only one showed IFX immunogenicity with newly developed ATIs at W30. Among ATI-positive patients at W0, ATI seroconversion from ATI-positive to ATI-negative status was observed in 10 of 17 patients (58.8%). Patients who had continued IFX-SC treatment at W30 showed significant decreases in C-reactive protein (P = .0341), fecal calprotectin (P = .0002), and Harvey-Bradshaw index (P = .0029) since W0. CONCLUSIONS: Patients with refractory CD previously treated with at least 2 biologics exhibited clinically relevant improvement with IFX-SC, which showed less immunogenic potential than IFX-IV and highly stable TL IFX.

Clinical and Research Center for Inflammatory Bowel Disease ISCARE and 1st Faculty of Medicine Charles University Prague Czech Republic

Department of Internal Medicine Hospital Jindrichuv Hradec Jindrichuv Hradec Czech Republic

Department of Internal Medicine Hospital of the Sisters of Mercy of St Charles Borromeo Prague Czech Republic

Department of Pediatrics University Hospital Motol and 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Surgery 3rd Faculty of Medicine Charles University and Kralovske Vinohrady University Hospital Prague Czech Republic

GENNET Prague Czech Republic

Institute of Animal Physiology and Genetics Czech Academy of Sciences Libechov Czech Republic

Institute of Pharmacology 1st Faculty of Medicine Charles University Prague Czech Republic

ResTrial GastroEndo Prague Czech Republic

Zobrazit více v PubMed

D’Amico F, Solitano V, Aletaha D, et al. . Biobetters in patients with immune-mediated inflammatory disorders: an international Delphi consensus. Autoimmun Rev. 2021;20(7):102849. PubMed

Alten R, An Y, Kim DH, Yoon SW, Peyrin-Biroulet L.. Re-routing infliximab therapy: subcutaneous infliximab opens a path towards greater convenience and clinical benefit. Clin Drug Investig. 2022;42(6):477-489. PubMed

Smith PJ, Critchley L, Storey D, et al. . Efficacy and safety of elective switching from intravenous to subcutaneous infliximab [CT-P13]: a multicentre cohort study. J Crohns Colitis. 2022;16(9):1436-1446. PubMed PMC

Schreiber S, Ben-Horin S, Alten R, et al. . Perspectives on subcutaneous infliximab for rheumatic diseases and inflammatory bowel disease: before, during, and after the COVID-19 era. Adv Ther. 2022;39(6):2342-2364. PubMed PMC

Huguet JM, García-Lorenzo V, Martí L, et al. . Subcutaneous infliximab [CT-P13], a true biologic 2.0. Real clinical practice multicentre study. Biomedicines. 2022;10(9):2130. PubMed PMC

Silverberg MS, Satsangi J, Ahmad T, et al. . Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. Can J Gastroenterol. 2005;19(1):5A-36A. PubMed

Harvey RF, Bradshaw MJ.. Measuring Crohn’s disease activity. Lancet. 1980;1(8178):1134-1135. PubMed

Rimola J, Ordás I, Rodriguez S, et al. . Magnetic resonance imaging for evaluation of Crohn’s disease: validation of parameters of severity and quantitative index of activity. Inflamm Bowel Dis. 2011;17(8):1759-1768. PubMed

Daperno M, D’Haens G, Van Assche G, et al. . Development and validation of a new, simplified endoscopic activity score for Crohn’s disease: the SES-CD. Gastrointest Endosc. 2004;60(4):505-512. PubMed

Kucharzik T, et al. ; STARDUST intestinal ultrasound study group. Early ultrasound response and progressive transmural remission after treatment with Ustekinumab in Crohn’s disease. Clin Gastroenterol Hepatol. 2023;21(1):153-163.e12. PubMed

Rutgeerts P, Sandborn WJ, Feagan BG, et al. . Infliximab for induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2005;353(23):2462-2476. PubMed

Peyrin-Biroulet L, Deltenre P, de Suray N, Branche J, Sandborn WJ, Colombel J-F.. Efficacy and safety of tumor necrosis factor antagonists in Crohn’s disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol. 2008;6(6):644-653. PubMed

Sprakes MB, Ford AC, Warren L, Greer D, Hamlin J.. Efficacy, tolerability, and predictors of response to infliximab therapy for Crohn’s disease: a large single centre experience. J Crohns Colitis 2012;6(2):143-153. PubMed

Ben-Horin S, Kopylov U, Chowers Y.. Optimizing anti-TNF treatments in inflammatory bowel disease. Autoimmun Rev. 2014;13(1):24-30. PubMed

Buhl S, Steenholdt C, Rasmussen M, et al. . Outcomes after primary infliximab treatment failure in inflammatory bowel disease. Inflamm Bowel Dis. 2017;23(7):1210-1217. PubMed

Sands BE, Anderson FH, Bernstein CN, et al. . Infliximab maintenance therapy for fistulizing Crohn’s disease. N Engl J Med. 2004;350(9):876-885. PubMed

Fine S, Papamichael K, Cheifetz AS.. Etiology and management of lack or loss of response to anti-tumor necrosis factor therapy in patients with inflammatory bowel disease. Gastroenterol Hepatol (N Y). 2019;15(12):656-665. PubMed PMC

Ungar B, Chowers Y, Yavzori M, et al. ; ABIRISK consortium. The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab. Gut. 2014;63(8):1258-1264. PubMed

Caron B, Fumery M, Netter P, Peyrin-Biroulet L.. Letter: treatment with subcutaneous CT-P13 in Crohn’s disease patients with intravenous infliximab failure. Aliment Pharmacol Ther. 2022;55(4):508-509. PubMed

Schreiber S, Ben-Horin S, Leszczyszyn J, et al. . Randomized controlled trial: subcutaneous vs intravenous infliximab CT-P13 maintenance in inflammatory bowel disease. Gastroenterology. 2021;160(7):2340-2353. PubMed

Subcutaneous infliximab in Crohn's disease patients with previous immunogenic failure of intravenous infliximab